Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Estrogen receptor β as drug target for the treatment of castrate resistant prostate cancer (#209)

Preetika Balanathan 1 , Shelley L Hedwards 1 , Michelle Richards 1 , Renea A Taylor 1 , David Pook 1 , Luc Furic 1 , Gail P Risbridger 1
  1. Monash University, Clayton, VIC, Australia

Several new therapies have recently become available for the treatment of castration-resistant prostate cancer (CRPC), however the disease remains incurable and demands novel therapeutic approaches. Selective estrogen receptor (ER) modulators are a class of drugs with mixed estrogen agonistic/antagonistic activity that holds promise in fulfilling this need. Although the expression and action of ERβ during PC progression has been unclear, we previously reported ERβ1 expression in human PC cell lines as well as in Gleason Grade 7 human specimens (1). Our data also showed the clinical significance of ERβ-induced action via specific agonist, 8β-VE2, by an increase in PC3-DsRed tumour doubling time (~2 fold) following 8β-VE2 treatment. We therefore hypothesized that ERβ agonists have therapeutic potential to prevent PC development and progression to CRPC.

This study initially characterized the expression of ERβ1 in CRPC TURP specimens (n=8). Nuclear ERβ staining was detected in 7/8 specimens and there was no difference in the staining in benign and cancer regions within the tissue. We further tested the therapeutic potential of ERβ activation by combining in vitro assays and in vivo imaging approaches; we analyzed the effects of 8β-VE2 on PC proliferation, apoptosis, and tumour growth using mcherry labelled PC cell lines. In vitro, ERβ agonists reduced proliferation and increased caspase 3 activity in androgen-dependent LNCaP cell line as well as in CR C4-2B cell line. Preliminarily analyzes of in vivo LNCaP and C4-2B tumour models show the potential of 8β-VE2 to slow PC development and progression using.

These data provide the evidence of ERβ expression in CRPC as well as functional data supporting the rationale for the potential use of ERβ agonist as new options for the treatment of CRPC.

  1. (1) McPherson et al., PNAS 2010; 107:3123